SAIL-MEVO: Endovascular Treatment Versus Best Medical Therapy for Distal Vessel Occlusions

Acute ischemic stroke due to medium and distal vessel occlusions (MeVOs) represents a substantial proportion of ischemic strokes. While endovascular treatment (EVT) is the standard of care for proximal large vessel occlusions, recent randomized trials have not demonstrated a consistent clinical benefit of EVT in MeVO populations. These neutral findings may reflect the heterogeneity of MeVO stroke, variability in patient selection, and differences in vascular anatomy and procedural complexity.

The SAIL-MEVO trial is an investigator-initiated, prospective, multicenter, randomized, open-label, blinded-endpoint (PROBE) trial designed to evaluate whether optimized EVT improves functional outcomes compared with best medical therapy (BMT) alone in carefully selected patients with acute ischemic stroke due to MeVO.

Participants aged 18 to 80 years presenting within 12 hours from symptom onset with an isolated distal vessel occlusion (non-dominant M2-M3 middle cerebral artery, A2-A3 anterior cerebral artery, or P2-P3 posterior cerebral artery), baseline NIHSS score between 9 and 17, ASPECTS ≥6, and an AI-predicted infarct core volume <10 mL on non-contrast CT will be eligible for enrollment.

Participants will be randomized in a 1:1 ratio to:

Best medical therapy (BMT) according to current stroke guidelines, including intravenous thrombolysis when indicated; or Best medical therapy plus endovascular treatment (EVT).

The EVT strategy consists of a standardized stepwise approach. Primary aspiration thrombectomy (ADAPT) will be performed first using a small-caliber distal aspiration catheter. If aspiration is unsuccessful or vascular anatomy prevents adequate catheter access, treatment will proceed using the SAIL technique, consisting of low-profile stent retriever deployment with localized intra-arterial thrombolysis according to the study operations manual.

The primary efficacy endpoint is functional independence, defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days after randomization.

Secondary efficacy endpoints include ordinal mRS shift, excellent functional outcome (mRS 0-1), early neurological improvement, infarct volume at 24-48 hours, discharge disposition, hospital length of stay, health-related quality of life (EQ-5D-5L), return to work or usual activities, and patient-reported outcome measures.

Safety endpoints include symptomatic intracranial hemorrhage, any intracranial hemorrhage, subarachnoid hemorrhage, embolization to new territory, vessel perforation or dissection, access-site complications, device- or procedure-related serious adverse events, all-cause mortality, and serious adverse events through 90 days.

Approximately 420 participants will be enrolled across up to 10 comprehensive stroke centers. Clinical outcomes will be assessed by investigators blinded to treatment allocation, and imaging endpoints will be adjudicated by an independent central imaging core laboratory. An independent Data and Safety Monitoring Board (DSMB) will oversee participant safety throughout the study.

• best medical therapy (Procedure): Guideline-based medical management for acute ischemic stroke, including intravenous thrombolysis when clinically indicated according to local and international stroke guidelines.
• Endovascular Treatment (Procedure): Endovascular treatment using a standardized stepwise protocol. Primary aspiration thrombectomy (ADAPT) is performed first using a small-caliber distal aspiration catheter. When aspiration is unsuccessful or vascular anatomy is unfavorable, treatment proceeds with the SAIL technique, consisting of deployment of a low-profile stent retriever with localized intra-arterial thrombolysis according to the study operations manual.

Primary outcomes

• Functional Independence at 90 Days [Assessment at 90 (±14) days after randomization]: Proportion of participants achieving functional independence, defined as a modified Rankin Scale (mRS, range 0 to 6, lower better) score of 0-2, assessed 90 (±14) days after randomization.

Secondary outcomes

• Ordinal Modified Rankin Scale (mRS) Score [Assessment at 90 (±14) days after randomization]: Distribution of modified Rankin Scale (mRS, range 0 to 6, lower better) scores
• Excellent Functional Outcome (mRS 0-1) [Assessment at 90 (±14) days after randomization]: Proportion of participants achieving a modified Rankin Scale (mRS, range 0-6, lower better) score of 0-1.
• Early Neurological Improvement [24 hours after randomization]: Proportion of patients acheiving an early neurological improvemente defined as a reduction in National Institute of Health Stroke Scale (NIHSS, range 0-42, lower better) score of ≥8 points from baseline or an absolute NIHSS ≤2 at 24 hours.
• Infarct Volume [24-48 hours after randomization]: Infarct volume measured by the central imaging core laboratory.
• Discharge Disposition [At hospital discharge (up to 15 days from randomization)]: Discharge to home versus rehabilitation or other healthcare facility.
• Length of Hospital Stay [At hospital discharge (up to 15 days from randomization)]: Duration of hospitalization measured in days.
• EQ-5D-5L Score [Assessment at 90 (±14) days after randomization]: Health-related quality of life assessed by the EQ-5D-5L ((EuroQol 5-Dimension, 5-Level), descriptive system and EQ VAS). Two components will be reported: the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions - mobility, self-care, usual activities, pain/discomfort, and anxiety/depression - each evaluated from 1 to 5 (no sumatory). A lower level on a dimension indicates better health. EQ VAS (vertical visual analogue scale: ranging from 0 - 100. Higher scores indicate better health)
• Return to Work or Usual Activities [Assesement at 90 days (+-14) after randomization]: Proportion of participants returning to work or usual daily activities.

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

* Age 18 to 80 years.
* Pre-stroke modified Rankin Scale (mRS) score of 0-1.
* Baseline NIH Stroke Scale (NIHSS) score between 9 and 17.
* Symptom onset to randomization less than 12 hours.
* Acute ischemic stroke due to an isolated medium/distal vessel occlusion involving a non-dominant M2-M3 middle cerebral artery, A2-A3 anterior cerebral artery, or P2-P3 posterior cerebral artery confirmed by CTA or MRA.
* Alberta Stroke Program Early CT Score (ASPECTS) ≥6 on non-contrast CT AND AI-predicted infarct core volume <10 mL on non-contrast CT (when available) AND AI-defined Tmax >6s volumen >30cc on CTP (when available).
* Written informed consent obtained from the participant or a legally authorized representative in accordance with local regulations.

Exclusion Criteria:

* Proximal large vessel occlusion (internal carotid artery or M1 segment) or tandem cervical internal carotid artery stenosis >70%.
* Intracranial hemorrhage at baseline imaging.
* Pregnancy.
* Life expectancy less than 3 months.
* Severe allergy to iodinated contrast media.

• Study Protocol: Protocol (PDF, 2026-09-08)
• Informed Consent Form: Next-of-kin/Representant informed consent (PDF, 2026-06-04)
• Informed Consent Form: patient (PDF, 2026-04-28)